Resistance of Gram-negative bacteria to aztreonam-avibactam: An evaluation of data from in vitro studies

Abstract

Introduction: Aztreonam-avibactam is a new combination antibiotic with a broad spectrum of activity against Enterobacterales and lactose non-fermenting Gram-negative bacteria. We evaluated the available data on resistance to aztreonam-avibactam.

Methods: We performed a thorough search of four databases for studies that included data on the antimicrobial susceptibility of Enterobacterales and lactose non-fermenting Gram-negative bacterial clinical isolates to aztreonam-avibactam. Data were grouped based on bacterial species (Enterobacterales and lactose non-fermenting Gram-negative bacteria) and whether the studied isolates were consecutive (non-selected) or selected. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint of resistance to aztreonam-avibactam for Enterobacterales (MIC > 4 mg/L) or the specific breakpoints reported by the authors for lactose non-fermenting Gram-negative bacteria were used.

Results: Seventy studies reported on in vitro susceptibility testing and mechanisms of antimicrobial resistance of a total of 520,606 clinical isolates (490,231 Enterobacterales and 30,375 lactose non-fermenting Gram-negative isolates). The proportion of Enterobacterales resistant to aztreonam-avibactam was very small in collections of consecutive (non-selected) isolates, specifically 0-1.8% across 7 studies, when a resistance breakpoint of MIC > 4 mg/L was used. Higher proportions of resistance were found in selected Enterobacterales isolates (34 studies), as well as in consecutive (2 studies) and selected (3 studies) lactose non-fermenting Gram-negative isolates, especially Acinetobacter baumannii.

Conclusion: The resistance of Enterobacterales clinical isolates to aztreonam-avibactam is rare. However, the noted resistance of selected Enterobacterales as well as consecutive and selected lactose non-fermenting Gram-negative isolates to aztreonam-avibactam suggests that its use should be based on in vitro antimicrobial susceptibility testing.

Keywords: Acinetobacter baumannii; Burkholderia cepacia; Enterobacterales; Lactose non-fermenting Gram-negative; Pseudomonas aeruginosa; metallo-β-lactamases.